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Antifungals Flashcards

(48 cards)

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1
Q

Amphotericin B

A

Antifungal (polyene)

cryptococcus meningitis w/ 5-FC; zygomycosis

IV-inpatient

binds to ergosterol and forms channels in fungal cell membrane, oxidative damage

Yeast and filamentous fungi:

Toxicity: nephrotoxicity and infusion related toxicity

Hepatic and renal excretion

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2
Q

Nystatin

A

Antifungal (polyene)

Topical candidiasis

Topical: oral, cutaneous, vaginal

binds to ergosterol and forms channels in fungal cell membrane, oxidative damage

*not systemically absorbed

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3
Q

Clotrimazole/Miconazole

A

Antifungal (azole)

topical - dermatophyte, candidiasis

inhibits lanosterol C-14 demethylase and ergosterol synthesis

*not systemically absorbed

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4
Q

Ketoconazole

A

Antifungal (azole)

shampoo for tinea capitis/tinea versicolor

topical; PO

inhibits lanosterol C-14 demethylase and ergosterol synthesis

Toxicity: hepatotoxic

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5
Q

Fluconazole

A

Antifungal (azole)

candidiasis; cryptococcus maintenance

PO, IV

inhibits lanosterol C-14 demethylase and ergosterol synthesis

Excretion: mostly renal and some hepatic

Toxicity: hepatotoxic

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6
Q

Itraconazole

A

Antifungal (azole)

endemic mycoses: Histo, Blasto, Cocci

PO

inhibits lanosterol C-14 demethylase and ergosterol synthesis

spectrum: yeasts and filamentous fungi

Toxicity: hepatotoxic

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7
Q

Voriconazole

A

Antifungal (azole)

Aspergillosis

PO/IV

inhibits lanosterol C-14 demethylase and ergosterol synthesis

spectrum: yeasts and filamentous fungi

Toxicity: hepatotoxic, hallucinations, rash

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8
Q

Posaconazole

A

Antifungal (azole)

2nd for aspergillosis; prophylaxis

PO

inhibits lanosterol C-14 demethylase and ergosterol synthesis

spectrum: yeasts and filamentous fungi

Toxicity: hepatotoxic

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9
Q

5-Flurocytosine

A

Antifungal (pyrimidine analog)

Cryptococcus w/ Amphotericin B

PO

inhibits thymidylate synthase and DNA/RNA synthesis

spectrum: yeasts

RENAL excretion

Toxicity: myelosuppression (pancytopenia), diarrhea, check AST and ALT

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10
Q

Terbinafine

A

Antifungal (allylamine)

Dermatophytes

PO, topical

inhibits squalene epoxidase and ergosterol synthesis

Toxicity: hepatotoxic

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11
Q

Caspofungin

Micafungin

Anidulafungin

A

Antifungal (echinocandin)

Candidemia, Aspergillus

IV

inhibits cell wall synthesis (1,3 beta glucan formation)

Toxicity: hepatotoxic

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12
Q

Trimethoprim-Sulfamethoxazole

TMP-SMX

A

Folic Acid Anti-Metabolites

Uses: UTI, respiratory, GI (sinusitis, otitis media)

trimethoprim: dihydrofolate reductase (50,000x more senstitive for bacterial enzyme)
sulfamethoxazole: mimic PABA- dihydropteroate synthetase (not in mammals)

*synergistic effects

PO-outpatient/IV - 2/3 daily doses

Spectrum: Broad: Gram negative, some protozoa and fungi,

more use against S. aureus

Excellent tissue penetration: urine, prostate, CSF

Resistance:

TMP: plasmid dhfr gene, transposons, integrons

SMX: plasmid, chromosomal mutation

Adverse Effects:

rash, nausea, vomiting, headache

hyperkalemia, hepatitis, pancreatitis

Stevens-Johnson syndrome, Toxic epidermal necrolysis, aplastic anemia, thrombocytopenia, hemolytic anemia

Pregnancy- kernicterus, displaces bilirubin from albumin

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13
Q

Ciprofloxacin

A

DNA Inhibitors- Fluroquinolone

Uses: UTI

DNA gyrase (topo II) creates supercoils; drug stabilizes enzyme-DNA complex with double stranded breaks-> chromosome fragmentation “bacteriocidal” genes gyr A and gyrB

PO-outpatient/IV BID

Spectrum: Gram negative, Atypicals, Mycobacteria

Good oral bioavailability

**Resistance: **

mutations in target enzyme gyrA, efflux pumps, plasmids

Adverse Effects:

safe, nausea, vomiting, abdominal pain

serious: prolongs QT interval in combination with other medications, tendon rupture, arthropathy??in children

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14
Q

Moxifloxacin

A

DNA Inhibitors- Fluroquinolone

Uses: pneumonia, mycobacterial

topo IV deconcatenates intertwined supercoils genes parC and parE

PO-outpatient/IV BID

Spectrum: Gram positive, Gram negative, Atypicals, Mycobacteria, Anaerobes

Good oral bioavailability; poor urinary penetration

NOT FOR UTIs

**Resistance: **

mutations in target enzyme parC, efflux pumps, plasmids

Adverse Effects:

safe, nausea, vomiting, abdominal pain

serious: prolongs QT interval in combination with other medications, tendon rupture, arthropathy??in children

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15
Q

Nitrofurantoin

A

DNA Inhibitors

UTIs FIRST LINE

relevant mechanism unclear

PO ONLY qID good urine levels

Spectrum: Gram negative, Gram positive uropathogens NOT pseudomonas, proteus, serratia, marcescens

Resistance rare but can develop with repeated use

Adverse effects: nausea, pulmonary fibrosis rare but can have acute pulmonary reactions

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16
Q

Rifampin

A

RNA Inhibitors

bind B subunit of RNA polymerase and block transcription, bacteriostatic

PO/IV qD-BID

Resistance due to mutations in binding pocket at 10-8, rapid due to mutations in target enzyme, frequenty pre-existing in population

Metabolism: potent inducer of P450 3A4

Spectrum: prophylaxis, N. meningitites, S. aureus, w/other antimicrobials for Mycobacterium infections

Adverse effects: turns secretions orange, GI- pain, nausea, vomiting, diarrhea, Heme- mild thrombocytopenia, Hepatits

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17
Q

Rifabutin

A

RNA Inhibitors

bind B subunit of RNA polymerase and block transcription, bacteriostatic

PO

Metabolism: less inducer of P450 3A4 but be aware

Spectrum: prophylaxis, N. meningitites, S. aureus, w/other antimicrobials for Mycobacterium infections

Adverse effects: turns secretions orange, GI- pain, nausea, vomiting, diarrhea, Heme- mild thrombocytopenia, Hepatits

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18
Q

Rifaximin

A

RNA Inhibitors

bind B subunit of RNA polymerase and block transcription, bacteriostatic

PO

*Not absorbed

Spectrum: GI: travelers’ diarrhea, C. difficile

Adverse effects: turns secretions orange, GI- pain, nausea, vomiting, diarrhea, Heme- mild thrombocytopenia, Hepatits

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19
Q

Fidaxomicin

A

RNA Inhibitors

blocks RNA polymerase, prevents formation of open DNA complex

*Not absorbed- PO

Spectrum: C. difficile

No serious side effects, very expensive, no resistance described

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20
Q

** Penicillin G**

Study These Flashcards
A

Penicillin

Uses: syphilis, strep A, B, pneumo, dental abscesses

IM/IV q4h IV, q12h IM w/procain, qweek w/ benzathine

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Resistance: penicillinase (B-lactamase)

Adverse: hypersensitivity, seizures in high doses

21
Q

** Ampicillin**

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A

Aminopenicillin

CAQ: HEENT, UTI

IV/PO q4-6h

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

R group more polar- penetration through gram negative porins- added H. flu, E. coli NOT pseudomonas

Spectrum: gram positive, more gram negative, some anaerobes

Resistance: penicillinase (B-lactamase)

Adverse: hypersensitivity, seizures in high doses

22
Q

** Amoxicilin**

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A

Aminopenicillin

CAQ: HEENT, UTI

NOT for mono-> maculopapular rash

PO TID

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

R group more polar- penetration through gram negative porins- added H. flu, E. coli NOT pseudomonas

Spectrum: gram positive, more gram negative (see above), some anaerobes

Resistance: penicillinase (B-lactamase)

Adverse: hypersensitivity, seizures in high doses

23
Q

** Nafcillin/Dicloxacillin**

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A

Semisynthetic penicillin

Uses: MSSA

nafcillin- IV q4-6hr dicloxacillin PO QID

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

bulky R group cant fit into many B-lactamases

Spectrum: GRAM POSITIVE ONLY, can’t penetrate Gram negative cell wall

Resistance: altered PBP, PBP2a encoded by mecA gene- MRSA

Adverse: hypersensitivity, seizures in high doses

24
Q

Piperacillin

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A

Antipseudomonal penicillin

Uses: Pseudomonas coverage

IV q4h

covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal

Spectrum: gram positive, gram-negative, Pseudomonas

Resistance limits use

Adverse: hypersensitivity, seizures in high doses

25
** Ampicilin-Sulbactam**
Aminopenicillin CAQ: HEENT, UTI IV q6h covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal R group more polar- penetration through gram negative porins- added H. flu, E. coli NOT pseudomonas Spectrum: gram positive, more gram negative (see above), some anaerobes **ADDED STAPHYLOCOCCUS and B-lactamase anaerobes** Adverse: hypersensitivity, seizures in high doses
26
** Amoxicilin-Clavulanic Acid**
Aminopenicillin CAQ: HEENT, UTI PO TID covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal R group more polar- penetration through gram negative porins- added H. flu, E. coli NOT pseudomonas Spectrum: gram positive, more gram negative (see above), some anaerobes **ADDED Staphylococcus and B-lactamase anaerobes** Adverse: hypersensitivity, seizures in high doses
27
**Piperacillin-Tazobactam**
Antipseudomonal penicillin Uses: Pseudomonas coverage IV q6h covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal Spectrum: gram positive, gram-negative, Pseudomonas **ADDED STAPHYLOCOCCUS and B-lactamase producing anaerobes** Adverse: hypersensitivity, seizures in high doses
28
**Cefazolin**
1st Gen Cephalosporin Uses: Surgical prophylaxis; skin. soft tissue infections IV q8h covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal Spectrum: gram positive, limited Gram negative Pseudomonas and Enterococci intrinsically resistant Generally well tolerated Some cross-reactivity with Penicillin allergy
29
**Cephalexin**
1st Gen Cephalosporin Uses: Surgical prophylaxis; skin. soft tissue infections PO QID covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal Spectrum: gram positive, limited Gram negative Pseudomonas and Enterococci intrinsically resistant Generally well tolerated Some cross-reactivity with Penicillin allergy
30
**Cefoxitin**
2nd Gen Cephalosporin Uses: intraabdominal surgery prophylaxis PO QID covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal Spectrum: gram positive, increasing Gram negative, excellent anaerobe Pseudomonas and Enterococci intrinsically resistant Generally well tolerated Some cross-reactivity with Penicillin allergy
31
**Ceftriaxone**
3rd Gen Cephalosporin Uses: serious infections; CAQ pneumonia, meningitis IV qD good tissue penentration, long half life covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal Spectrum: gram positive, excellent Gram negative Pseudomonas and Enterococci intrinsically resistant Generally well tolerated Some cross-reactivity with Penicillin allergy
32
**Ceftazidime**
3rd Gen Cephalosporin Uses: Activity against PSEUDOMONAS IV qD good tissue penentration, long half life covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal Spectrum: gram positive, excellent Gram negative Enterococci intrinsically resistant Generally well tolerated Some cross-reactivity with Penicillin allergy
33
**Ceftazidime**
4th Gen Cephalosporin Uses: serious infections IV q12h good tissue penentration, long half life Spectrum: broad: gram positive, excellent Gram negative INCLUDING PSEUDOMONAS Very resistant to B-lactamases, Enterococci intrinsically resistant Generally well tolerated Some cross-reactivity with Penicillin allergy covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal
34
**Ceftaroline**
5th Gen Cephalosporin Uses: serious infections IV good tissue penentration, long half life Spectrum: broad: gram positive INCLUDING MRSA, Gram negative W/O pseudomonas BInds PBP2a, very resistant to B-lactamases, Enterococci intrinsically resistant Generally well tolerated Some cross-reactivity with Penicillin allergy covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal
35
**Aztreonam**
Monobactam Uses: B-lactam allergy, limited IV q8h Spectrum: GRAM NEG ONLY covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal
36
**Imipenem** **Doripenem** **Ertapenem**
Carbapenems Uses: empiric treatment for serious infections, resistant infections IV q8h Spectrum: BROAD Gram positive, Gram negative including pseudomonas, anaerobes Resistance: typically resistant to B-lactamases, emergence of carbapenem-hydrolyzing B-lactamases covalent irreversible attachment to transpeptidase, osmotic lysis, bacteriocidal \*\*ertapenem- doesn't have activity against pseudomonas or acinetobacter
37
**Vancomycin**
Glycopeptides Uses: inferior to B-lactams, empiric treatment for serious infections, resistant Gram positive Oral C. Diff infection IV q12h (\*renally excreted, dose adjustment) binds to terminal D-ala, D-ala inhibits cell wall synthesis transglycosylase and transpeptidase, bactericidal Spectrum: GRAM POSITIVE ONLY: MRSA, enterococci, GP anaerobes, streptococcus Resistance:vanA-E changes NAM terminal peptide VISA- thickened cell wall, dec penetration Adverse Effects: Red Man Syndrome- infusion reaction, nephrotoxic, dose-dependent ototoxicity
38
**Daptomycin**
Cyclic Lipopeptide Uses: complicated GP infections, skin/soft tissue infections, bacteremia/endocarditis IV q24hr lipid tail inserts into cell mbr, mem depol./K efflux, cessation of vital processes, cell death w/o lysis; bactericidial Spectrum: ONLY GRAM POS, includes MRSA, enterococci VRE, GP anaerobes Adverse Effects: GI, headache, elevated **CPK/rhabdomyolysis (monitor, avoid statins)**
39
**Polymyxin B**
Other Uses: serious- GN , inhaled resistant GN pneumonia IV q12hr Spectrum: GRAM NEGATIVE ONLY Adverse Effects: significant toxicities (nephrotoxicity, neurotoxic, inhaled -\>bronchospasm)
40
**Bacitracin**
Other topical GRAM POSITIVE only Strep pyogenes, Staph
41
**Fosfomycin**
Other: UTI oral powder 1 dose GRAM POS AND GRAM NEG
42
**Amikacin / Gentamicin**
Aminogylcosides, IV only Mech: binds 30S subunit causing misreading/terminates genetic code Spectrum: primarily GN (**includes Pseudomonas**) no anaerobes, Other: MB, Yersinia pestis, Francisella tularensis \*\*synergy with B-lactams, allow aminoglycosides to enter gram positive cell wall PK/PD: bactericidal or static depending on concentration; inhibited by acidic environment does not work in the lungs Adverse Effects: ototoxicity, nephrotoxicity, neuromuscular blockade
43
**Doxycycline**
Tetracycline Mech: binds 30S subunit reversibly blocks access of tRNA to mRNA Uses: bronchitis, CAQ pneumonia, STDs- chlamydia, lyme, leptospirosis, malaria prophylaxis Spectrum: GN, GP, anaerobic, atypicals: chlamydia, mycoplasma Resistance: efflux pumps and ribosomal protection proteins PK/PD: bacteriostatic; absorption inhibited by Ca \*\*binds to tissues undergoing calcification (bones, teeth) NOT for kids or PG women Adverse Effects: deposition in bone, teeth, photosensitivity
44
**Tigecycline**
Synthetic derivative tetracycline, IV only Mech: binds 30S subunit structural modifications overcome a lot of resistance Uses: complicated skin/soft tissue infections; CAQ pneumonia, intraabdominal infections Spectrum: GN, GP (MRSA, VRE), anaerobic Adverse Effects: black box increased mortality risk
45
**Azithromycin Clarithromycin Erythromycin**
Macrolides Mech: binds 50S subunit, blocks translocation Uses: \*\* azithro- CAQ pneumonia/bronchitis, chlamydia, travellers diarrhea, MAC prophylaxis \*\*erythro- gut motility, prokinetic \*\*clarithromycin- Mycobacterium avium, H. pylori Spectrum: GN, GP, some GN anaerobes, Atypicals: mycoplasma, legionella, chlamydia Resistance: (4) decreased permeability, efflux pumps, target site alteration (erm gene), enzymatic drug inactivation PK/PD: static, widely distributed in tissues, erythro CYP450 Adverse Effects: N/V/D -- prolonged QT
46
**Clindamycin**
Macrolides Mech: binds 50S subunit, blocks translocation Uses: CAQ pneumonia, oral HEENT, human bites, abscesses, soft tissue/skin infections Spectrum: ONLY GP, above diapraghm anaerobes Resistance: target site alteration (erm gene), S. aureus- worry about erythromycin resistance inducing clinda resistance PK/PD: cidal, widely distributed in tissues except CNS Adverse Effects: C. difficile associated disease
47
**Linezolid**
Oxazolidinones Mech: binds 50S subunit, prevents formation of 70S complex Uses: VRE, MRSA, complicated skin/soft tissue infections Spectrum: ONLY GP, other Mycobacteria Resistance: uncommon, acquire cfr plasmid PK/PD: static, 100% bioavailable Adverse Effects: bone marrow suppression, thrombocytopenia, inhibits MOA- serotonin syndrome
48
**Mupirocin**
Mech: unique Uses: VRE, MRSA, complicated skin/soft tissue infections Spectrum: ONLY GP, other Mycobacteria Resistance: uncommon, acquire cfr plasmid PK/PD: static, 100% bioavailable Adverse Effects: bone marrow suppression, thrombocytopenia, inhibits MOA- serotonin syndrome

Antibiotics (8 decks)

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